Medication Sticks & Suppositories Flashcards
What are some pharamceutical application for medication sticks?
- Pain relief (Hot-Cold Therapy)
- Lip Balms (ex. Blistex)
- Specialty compounds
Why are medication sticks less commonly prepared these days?
Other dosage forms like creams have better efficacy
What are the two main categories for medication sticks?
Soft Sticks
Hard Sticks
What are some characteristics of soft sticks?
- Use amorphous solids for the base (has range of melting points)
- Convienent to apply topical drugs
ex. Lip balm
What are some characteristics of hard sticks?
- Crystalline powder fused by heat or held together with binders such as petrolatum
- Moisture is needed to activate
- Not used for most pharmaceutical applications anymore unless as specialty compounds
What are two types of bases used in medication stick formulations?
Fatty bases:
- Fatty bases (Vegetable oils, cocoa butter)
Water-soluble bases:
- Sodium stearate, glycerol PEGs
Are suppositories a common dosage form?
Not really. Only 1% of drugs are formulated into suppositories
Are suppositories only capable of local effect?
No, rectal delivery systems like suppositories can be used for systemic and local effects
What are some examples of suppositories?
- Acetaminophen (systemic)
- Diclofenac (systemic)
- Preparation H (Anesthetic/HC with local effects)
What is the definition of a suppository?
- A solid dosage form used for rectal, vaginal, urethral administration
- Consists of a dispersion of API in an inert matrix (rigid or semi-rigid base)
What are some advantages of suppositories over other dosage forms?
- Less invasive than injectables
- Quicker onset of effect for GI conditions
- Limit drug interactions when given in combination with other therapies
- Higher bioavailability because it bypasses first-pass effects
- Can be used for both local and systemic effects
- Accomodates administration in unconscious patients or infants (or have difficulty swallowing pills)
What are the limitations of suppositories vs. other dosage forms?
- Low patient acceptance
- Less common dosage form
- Special storage conditions (low temp to prevent base from melting)
What are some characteristics of the rectal environment?
The rectum is relatively constant and static in comparison to other parts of the gastrointestinal tract
- Average fluid volume: 1-3 mL
- Neutral pH of 7-8, with minimal buffering capacity
- Biotransformation by enzymes in the rectim is not significant
- Relatively small surface area for absorption vs. the small intestine
- Good vasculature that improves F due to some of the absorbed materials reaching the systemic circulation without entering the liver)
What happens to drugs that are absorbed in the rectum?
- Inferior/middle rectal vein drain into the inferior vena cava (directly into the systemic circulation)
- Superior rectal veins drain into the portal vein, which passes blood and its absorbed contenct through the blood where drug is subject to bitransformation)
What are some drug factors that impact the formulation of suppositories?
- Partition coefficient (ex. high partition coefficient (slow release from fatty base, and quick release from hydrophillic bases
- Physical state of the drug in the formulation
- Solubility (degree of ioniziation and particle size)
a. Drug solubility
b. Acid-dissociation constant (pKa) (unionized vs. ionized)
c. Particle size (smaller partices have better absorption than larger ones)
What are some physiological factors that impact the absorption of drug from the rectum?
- Anatomical size (kids have smaller bodies than adults)
- Site of drug delivery in the rectum (has an impact on F, but it is a non-controllable factor)
- Changes in pH (damage to rectal mucosa)
- Presence of stool in the rectum affects the viscosity of the rectal contents (impacts drug dissolution, stability, and contact area with mucosal surface)
- Bowel movement frequency (affect contact time)
- Pathological changes in tissue integrity (increased mucosal membrane thicening in response can make drug response unpredictable or painful admin due to inflammation)
What are the main locations where suppositories are inserted into?
- Rectal
- Vaginal
- Urethral
What are some drug characteristics that are best suited for suppositories?
- Poorly absorpting orally
- Taste unacceptable (ex. Glycerin)
- Irritation to GI mucosa
- Drug of abuse (smaller doses when given rectally)
- Acid labile drugs
- Drugs prone to enzymatic degradation
What are soem vehicle characteristics that are best suited for suppositories?
Vehicle should be able to:
- Melt
- Soften
- Dissolve at body temperature
- Promote drug release
- Stay stable during manufacturing and storage
- Inert
- Esthetically acceptable
What are some bases used in suppositories?
Fatty bases:
- cocoa butter
- hydrogenated vegetable or palm oil
Water-soluble bases:
- Glycerine based suppositories
- PEG
For drugs that are hydrophillic, should we use a hydrophillic base for optimal release of drug from vehicle?
No, the polarity of the base must be in opposition of the drug’s polarity
ex. Hydrophillic drug in lipophillic base
When using cocoa butter as a base, what are some unique characteristics?
- Low melting temperature (31-35*C)
- Four major polymorphic forms (variation in melting points)
- It requires lubrication of the mold (sticky character)
When using hydrogenated oils as a base, what are some unique characteristics?
- Semi-synthetic, waxy solids
- No polymorphisms (less variation in melting point)
- More resistant to oxidation and hydrolysis)
- Lower viscosity (increased separation risk, can lead to lack of uniformity)
What are some concerns with water soluble bases?
They are not inert (they have laxative effect). Can only use if laxative activity is intended
Storage conditons are strict
What are some characteristics of PEG as a suppository base?
- Hydrophillic base
- Used as combination of PEG with different melting points
What are some commonly used additives in suppository preparations?
Fixed oils and water (depending on drug polarity) can act as levigating agents
Surfactants (increase hydrophillicity and dissolution characteristics)
Antimicrobial, antifugal, antioxidants all protect against degradation
Are oral dosage forms more bioavailable compared to rectal preparations?
No, rectal route is preferential for increased bioavailability
What are some patient groups who may benefit from rectal route of administration?
- Pediatric patients
- Patients facing dysphagia (difficulty swallowing)
- Refusing oral medications or spitting out tabs
- Patients with GI obstruction
- Loss of conciousness/palliative care
- Patients with decreased mental status
What are some situations where one should not cnsider rectal route of administration?
- Neonatal patients
- Patients who may have conditions associated with neutropenia (due infection risk)
- Chronic constipation
- Increased GI motility
- Dosage form insertion causes pain
What are the general suppository compounding steps?
- Mold preparation
- Mold calibration
- Base preparation
- Incorporation of active drug (displacement factor)
- Mixing and pouring
- Cooling and finishing
- Packaging, storage, and labelling
What is the displacement factor when preparing suppositories?
It is a measure of active substance that displaces 1g of suppository
It is significant due to its impact on final suppository weight and dosing uniformity (especially for high displacement factor drugs)
What are the three processes that are used to form suppositories?
- Moulding (fusion of ingredients and pour into mould)
- Compression
- Hand rolling
What is the most common extemporaneous technique to prepare suppositories?
Compression
MIx API with base and place into compression mechanism. Allow mixture to be extruded from compression mechanism. Cut extruded mixture for desired dose amounts. Shape these fragments into suppositories
What are some characteristics of hand rolling as a technique for suppository preparation?
- Does not require special calculation
- Mostly for cocoa butter
- Tedious, requires experience
- Not very uniform
What are some storage requirements for suppositories?
- Must be packaged individually
- Fatty bases (store in a cool place 2-8*C)
- Water-washable bases (Tightly closed containers to prevent moisture absorption)
What are the main product quality issues that can impact suppositories?
- Splitting, pitting, and cracking
- Sticking to mould
- Poor product homogeneity
Review slide 46 for a more comprehensive list includeing causes and solutions
Can lubricants be used before inserting suppositories?
Yes, but avoid hydrophobic bases like petrolatum jelly. They will limit absorption from the vehicle and into the body
What are some counselling tips for suppositories?
- Follow package insert instructions
- Insert medication about a finger’s length into the rectum and place against the rectum wall
- Close your legs and sit still for about 15 min
- Avoid bowel movement for atleast 1 hour
- Vaginal suppositories often come with an applicator for proper insertion
